Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

Handle URI:
http://hdl.handle.net/10754/596772
Title:
Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.
Authors:
Lovrics, Anna; Gao, Yu; Juhász, Bianka; Bock, István; Byrne, Helen M; Dinnyés, András; Kovács, Krisztián A
Abstract:
We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.
Citation:
Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, et al. (2014) Boolean Modelling Reveals New Regulatory Connections between Transcription Factors Orchestrating the Development of the Ventral Spinal Cord. PLoS ONE 9: e111430. Available: http://dx.doi.org/10.1371/journal.pone.0111430.
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS ONE
KAUST Grant Number:
KUK-C1-013-04
Issue Date:
14-Nov-2014
DOI:
10.1371/journal.pone.0111430
PubMed ID:
25398016
PubMed Central ID:
PMC4232242
Type:
Article
ISSN:
1932-6203
Sponsors:
This publication was based on work supported in part by IDPbyNMR, PluriSys, InduStem, RESOLVE, EpiHealth, Stem-Cam, ANISTEM (grant agreement numbers PITN-GA-2010-264257, HEALTH-F4-2009-223485, PIAP-GA-2008-230675, FP7-HEALTH-F4-2008-202047, HEALTH-2012-F2-278418, PIAP-GA-2009-251186, PIAPP-GA-2011-286264) projects funded by the EC Seventh Framework Programme, Research Centre of Excellence, 8526-5/2014/TUDPOL, Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST) and the IST FELLOWSHIP awarded to Krisztian A Kovacs (Project: P IST EU01 under REA grant agreement no 291734). Al, YG, BJ and KK were affiliated to Biotalentum Ltd. IB and AD are still affiliated to Biotalentum Ltd, and received salary from them to support this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Appears in Collections:
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Full metadata record

DC FieldValue Language
dc.contributor.authorLovrics, Annaen
dc.contributor.authorGao, Yuen
dc.contributor.authorJuhász, Biankaen
dc.contributor.authorBock, Istvánen
dc.contributor.authorByrne, Helen Men
dc.contributor.authorDinnyés, Andrásen
dc.contributor.authorKovács, Krisztián Aen
dc.date.accessioned2016-02-21T08:50:22Zen
dc.date.available2016-02-21T08:50:22Zen
dc.date.issued2014-11-14en
dc.identifier.citationLovrics A, Gao Y, Juhász B, Bock I, Byrne HM, et al. (2014) Boolean Modelling Reveals New Regulatory Connections between Transcription Factors Orchestrating the Development of the Ventral Spinal Cord. PLoS ONE 9: e111430. Available: http://dx.doi.org/10.1371/journal.pone.0111430.en
dc.identifier.issn1932-6203en
dc.identifier.pmid25398016en
dc.identifier.doi10.1371/journal.pone.0111430en
dc.identifier.urihttp://hdl.handle.net/10754/596772en
dc.description.abstractWe have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.en
dc.description.sponsorshipThis publication was based on work supported in part by IDPbyNMR, PluriSys, InduStem, RESOLVE, EpiHealth, Stem-Cam, ANISTEM (grant agreement numbers PITN-GA-2010-264257, HEALTH-F4-2009-223485, PIAP-GA-2008-230675, FP7-HEALTH-F4-2008-202047, HEALTH-2012-F2-278418, PIAP-GA-2009-251186, PIAPP-GA-2011-286264) projects funded by the EC Seventh Framework Programme, Research Centre of Excellence, 8526-5/2014/TUDPOL, Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST) and the IST FELLOWSHIP awarded to Krisztian A Kovacs (Project: P IST EU01 under REA grant agreement no 291734). Al, YG, BJ and KK were affiliated to Biotalentum Ltd. IB and AD are still affiliated to Biotalentum Ltd, and received salary from them to support this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.publisherPublic Library of Science (PLoS)en
dc.rightsThis is an open-access article distributed under the terms of the , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subject.meshModels, Geneticen
dc.subject.meshGene Regulatory Networksen
dc.titleBoolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.en
dc.typeArticleen
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC4232242en
dc.contributor.institutionBiotalentum Ltd., Gödöllö, Hungary.en
dc.contributor.institutionBiotalentum Ltd., Gödöllö, Hungary; Molecular Animal Biotechnology Laboratory, Szent Istvan University, Gödöllö, Hungary.en
dc.contributor.institutionOxford Centre for Collaborative Applied Mathematics, Mathematical Institute, University of Oxford, Oxford, United Kingdom.en
dc.contributor.institutionBiotalentum Ltd., Gödöllö, Hungary; Molecular Animal Biotechnology Laboratory, Szent Istvan University, Gödöllö, Hungary; Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.en
dc.contributor.institutionBiotalentum Ltd., Gödöllö, Hungary; Institute of Science and Technology, Klosterneuburg, Austria.en
kaust.grant.numberKUK-C1-013-04en

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